Bacterial or yeast vaginitis is a common and noxious condition that at one time or another affects nearly all women. In a minority of women of reproductive age, it recurs or persists, usually for unknown reasons. Moreover, overgrowth of various microbial species in the vagina has been implicated in prematurity and low birth weight with its attendant complications. The interaction between host defense systems in the vagina and resident or exogenous microbes has not been adequately studied. The vaginal epithelium is covered by a thin layer of fluid that forms a potential barrier to microbial colonization, adherence and invasion. Based on preliminary data, and our studies in other epithelia, we hypothesize that this fluid contains antimicrobial polypeptides that mediate the resistance of the vaginal epithelium to invasion by microorganisms, defend lesions generated by microtrauma, and regulate the composition of the vaginal microflora by selective toxicity to exogenous microbes. Genetic or acquired disturbances in the composition of this fluid may result in increased susceptibility to colonization by endogenous or exogenous microbial species. To explore this hypothesis, the following specific aims are proposed: 1. Identify the principal polypeptides of human vaginal secretions 2. Analyze the antimicrobial spectrum and interactions of the most active components 3. Characterize the regulation of each component during the menstrual cycle 4. Search for abnormalities in the polypeptide composition of vaginal fluid in patients with vaginitis/vaginosis In the aggregate, these specific aims will provide a comprehensive framework for understanding the role of epithelial fluid in innate host defense of the vagina. In the longer term, replacement of missing or defective components of vaginal fluid should be an effective strategy for the prevention or treatment of vaginitis/vaginosis and other vaginal infections, and their attendant complications.